Bo Yan

Bio: Bo Yan is an academic researcher from Shanghai Jiao Tong University. The author has contributed to research in topics: Lung cancer & Medicine. The author has an hindex of 6, co-authored 19 publications receiving 154 citations. Previous affiliations of Bo Yan include Fudan University.

Circular RNA ciRS-7 correlates with advance disease and poor prognosis, and its down-regulation inhibits cells proliferation while induces cells apoptosis in non-small cell lung cancer.

Abstract: Objective This study aimed to assess the association of circular RNA (circRNA) ciRS-7 expression with clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients, and to investigate its effect on cells proliferation as well as apoptosis in NSCLC. Patients and methods 132 patients with primary NSCLC who received surgical resection were recruited in this retrospective study. All patients' tumor tissue and paired adjacent tissue were collected for circRNA ciRS-7 expression detection by RT-qPCR. Disease-free survival (DFS) and overall survival (OS) were calculated. CCK-8 and Annexin-V/propidium iodide (AV/PI) assays were performed to detect cells proliferation and apoptosis in A549 cells after circRNA ciRS-7 inhibition plasmid transfection. Results CircRNA ciRS-7 expression in tumor tissue was elevated compared to paired adjacent tissue, and positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stages. K-M curves illustrated that circRNA ciRS-7 high expression was correlated with both shorter DFS and OS, and multivariate Cox's proportional hazards regression analysis showed that circRNA ciRS-7 high expression was an independent factor for predicting unfavorable DFS and OS. Cells methods revealed that circRNA ciRS-7 expression was elevated in NSCLC cell lines (A549, PC9, NCI-H1299 and NCI-H1650) compared to normal lung epithelial cells (DEAS-2B), and the inhibition of circRNA ciRS-7 expression reduced cells proliferation and promoted cells apoptosis in A549 cells. Conclusions CircRNA ciRS-7 overexpression is associated with advanced disease and poor prognosis in NSCLC patients, and the down-regulation of circRNA ciRS-7 inhibits tumor cells proliferation as well as improves cells apoptosis.

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies.

Abstract: This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447-0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.

Circulating DNA-Based Sequencing Guided Anlotinib Therapy in Non-Small Cell Lung Cancer.

Abstract: Anlotinib is a multitargeted antiangiogenic drug, and its clinical predictor for responsive non-small cell lung cancer (NSCLC) patients is still elusive. Here, tumor-specific target capture is used to profile the circulating DNA of ALTER0303 (evaluating NSCLC clinical antitumor efficacy through anlotinib therapy) study participants. The results indicate that patients receiving no benefit can be mainly excluded via analysis of ARID1A and BRCA2 genetic profiling. For patients with no durable benefit and durable clinical benefit patients, three predictors: germline and somatic mutation burden (G+S MB), nonsynonymous and synonymous mutation burden (N+S MB), and unfavorable mutation score of circulating DNA profiling are identified. Through integrating the advantages and disadvantages of three independent predictors, the tumor mutation index (TMI) is established as a prediction model and the patients who are very likely to benefit more from anlotinib therapy are identified. Furthermore, the IDH1 exon 4 mutation is identified as an unfavorable factor for anlotinib therapy under TMI-based stratification, and the TMI plus IDH1 exon 4 mutation status potentially predicts response to anlotinib. Collectively, this study provides a circulating DNA sequencing-based stratification method for identifying anlotinib responders via a noninvasive approach, and thus potentially improves the clinical outcome of NSCLC patients receiving third-line therapy.

Reduced E-Cadherin expression is a prognostic biomarker of non-small cell lung cancer: a meta-analysis based on 2395 subjects.

Abstract: Objective: Previous studies related to the prognostic value of E-Cadherin expression on non-small cell lung cancer (NSCLC) were inconsistent. The present study aimed to evaluate the relation between E-Cadherin expression and the prognosis of NSCLC. Methods: We performed a meta-analysis based on 14 studies including 2395 NSCLC patients. Literature retrieval, data extraction, and meta-analyses were performed according to the Revman 5.0 guidelines. We utilized the fixed-effect model to pool the HR according to the test of heterogeneity in the meta-analysis. Results: A total of 14 eligible studies including 2395 NSCLC patients were analyzed. In total, 51.2% of the patients were considered as having reduced expression of E-Cadherin according to the authors’ cutoff. The pooled hazard ratio (HR) of reduced expression of E-Cadherin for overall survival (OS) was 1.19 (95% CI: 1.01 to 1.40, P=0.04), showing a worse survival when E-Cadherin expression is decreased. Conclusion: Patients with reduced expression of E-cadherin have a poorer OS compared with those with normal or high expression of E-cadherin.

Different characteristics and survival in non-small cell lung cancer patients with primary and acquired EGFR T790M mutation.

Abstract: Primary epidermal growth factor receptor (EGFR) T790M mutation can be occasionally identified in previous untreated nonsmall cell lung cancer (NSCLC) patients. To compare clinical characteristics and outcomes in patients with primary and acquired EGFR T790M mutation, we collected the data of patients diagnosed with EGFR mutation from 2012 to 2017 in Shanghai Chest Hospital. Primary EGFR T790M mutation was identified in 61 patients (1.1%; 95% confidence interval (CI): 0.8%-1.3%) of 5685 TKI-naive EGFR mutant patients. Acquired T790M mutation was detected in 98 patients (50.3%; 95%CI: 43.2%-57.3%) of 195 TKI-treated patients. T790M mutation always coexisted with sensitizing EGFR mutations. Primary EGFR T790M always coexisted with 21L858R (46/61) whereas acquired T790M coexisted with 19del (68/98), (p < 0.001). Among them, 18 patients with primary T790M mutation received osimertinib and 72 patients with acquired T790M mutation received osimertinib. The median progression-free survival (PFS) of osimertinib was significantly longer in primary T790M group (17.0 months, 95%CI:14.0-20.0 months) compared to acquired T790M group (10.0 months, 95%CI:8.6-11.4 months, p = 0.022). However, the median overall survival (OS) of acquired T790M mutation patients was significantly longer compared to that of primary T790M mutation patients who received osimertinib (50.4 months vs. 29.9 months, p = 0.016). Our findings suggest that primary T790M mutation likely coexists with 21L858R while acquired mutation likely coexists with 19del. Both mutations showed good response to osimertinib. Patients with primary T790M mutation experienced greater benefits from osimertinib. However, patients with acquired T790M mutation had a better overall survival during the entire clinical treatment.

Cancer health disparities in racial/ethnic minorities in the United States

Abstract: There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.

CircRNA-ENO1 promoted glycolysis and tumor progression in lung adenocarcinoma through upregulating its host gene ENO1

Abstract: Lung adenocarcinoma (LUAD) has long been one of the predominant reasons for the global cancer-linked mortality. The tumor progression is shown by several studies to be promoted by increased glycolysis. Enolase 1 (ENO1), as a glycolysis enzyme, performs pivotal role in glucose metabolism and contributes to tumor progression of numerous cancers. Circular RNAs (circRNAs) are catching increasing attentions for their surging roles in regulating gene expression in cancers. Our work is to uncover the regulatory mechanism circ-ENO1 on its host gene ENO1 and its function in glycolysis and tumor progression. Circ-ENO1 and its host gene ENO1 were identified to be upregulated in LUAD cells. Functionally, silencing circ-ENO1 retarded glycolysis, inhibited proliferation, migration and EMT, induced apoptosis. The cytoplasmic localization of circ-ENO1 was determined by FISH and subcellular fractionation. Mechanistically, circ-ENO1 acted as a ceRNA to interact with miR-22-3p and upregulate ENO1 expression. In vivo experiments certified that circ-ENO1 drove tumor growth and metastasis in vivo. In summary, current study elucidated that circ-ENO1 promoted glycolysis and tumor progression in LUAD by miR-22-3p/ENO1 axis, indicating circ-ENO1 as a promising treatment target for LUAD patients.

Activation of NLRP3 inflammasome enhances the proliferation and migration of A549 lung cancer cells

Abstract: Lung cancer is the leading cause of cancer death, and it is widely accepted that chronic inflammation is an important risk for the development of lung cancer. Now, it is recognized that the nucleotide-binding and oligomerization domain (NOD) like receptors (NLRs)-containing inflammasomes are involved in cancer-related inflammation. This study was designed to investigate the effects of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome on the proliferation and migration of lung adenocarcinoma cell line A549. Using 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, scratch assay, and Transwell migration assay, we showed that activation of the NLRP3 inflammasome by LPS+ATP enhanced the proliferation and migration of A549 cells. Western blot analysis showed that activation of phosphorylation of Akt, ERK1/2, CREB and the expression of Snail increased, while the expression of E-cadherin decreased after the activation of NLRP3 inflammasome. Moreover, these effects were inhibited by the following treatments: i) downregulating the expression of NLRP3 by short hairpin RNA (shRNA) interference, ii) inhibiting the activation of NLRP3 inflammasome with a caspase-1 inhibitor, iii) blocking the interleukin-1β (IL-1β) and IL-18 signal transduction with IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP). Collectively, these results indicate that NLRP3 inflammasome plays a vital role in regulating the proliferation and migration of A549 cells and it might be a potential target for the treatment of lung cancer.

Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance

Abstract: Activating mutations in the epidermal growth factor receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20–30% of patients do not respond or respond for a very short time (<3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined by analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent in EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.